Characteristics and Safety Profile in Patient Received Ixazomib in China: Interim Analysis of a National, Prospective, Non-Interventional Study of Using Ixazomib in Real-World Clinical Practice (INFINITE Study)

Background: China Food and Drug Administration formally approved the marketing of imported Ixazomib Citrate capsules in China on Apr 25, 2018. Pre-marketing clinical research was conducted restrictively in relapsed refractory multiple myeloma (RRMM) patients (pts) with multiple exclusion criteria and was not a comprehensive reflection of Ixazomib (IXA) real-world pts safety circumstances. Therefore, it is necessary to conduct a prospective post-marketing study to understand the gap between real clinical practice and pre-marketing clinical research.

Aim: To report the characteristics and safety profile of IXA in Chinese multiple myeloma pts. We report an interim analysis (IA) of the INFINITE study.

Method: INFINITE Study (NCT04328662) is a prospective, non-interventional, single-country study. Pts who have received at least one dose of IXA-based regimen treatment, with IXA < 3 months from their initial treatment or will be prescribed were included in the study. The enrolled pts with RRMM who received at least one dose of IXA-lenalidomide-dexamethasone (IRd) treatment were assigned to cohort 1. The newly diagnosed multiple myeloma (NDMM) and non-myeloma pts who have received at least one dose of IXA-based regimen, and RRMM pts who have received at least one dose of non-IRd IXA-based treatment were assigned to cohort 2. The primary outcome of this analysis is to evaluate the safety profile of IXA in a Chinese patient population. The secondary outcomes are effectiveness (ORR, DOT, TTNT, PFS, OS) of IXA in RRMM patients, safety, and efficacy based on clinical / disease characteristics as defined in cohort 1 and cohort 2. The time to event outcomes was estimated by the Kaplan-Meier method for incomplete observations and all statistical analysis were performed using SAS Enterprise Guide 8.3 software.

Results: As of 31 Jan 2022 (data cut-off), 114 pts (Cohort 1 (n=6); Cohort 2 (n=108)) were enrolled and considered for data analysis. Among these, 10 pts had discontinued/withdrew from the study (1 pts due to disease progression, 2 pts due to death, 7 pts for other reasons). On overall evaluation at baseline 114 pts have been treated with IXA; median age 65 yrs [range 34-89]; 59.6% male; 35.1% with ISS III disease; 26.3% with R-ISS III disease; 62.3% with Durie-Salmon stage III; 32.5% with high-risk by Stratification of Mayo mSMART guidelines; 15.8% patient received stem cell transplantation. 78.9/17.5/7.0/ 2.6% pts had received prior treatment in L1/L2/L3/other respectively, before IXA. Further, 64 %pts received a V-based regimen including VCD/VRD/VTD in first-line therapy. Route of bortezomib administration was by intravenous injection and subcutaneous injection in 21.9% and 48.2% pts respectively, with the rest unknown. At baseline evaluation, 2.6/7.9/8.8/4.4% pts had achieved sCR/CR/VGPR/PR (Table 1). At the time of this IA, median follow-up is 4.01 month, 91.2% (104/114) of pts were still on therapy and enrollment is ongoing. Median duration from the start of IXA-based treatment was 3.5 months. The median time to next treatment was 3.8 months. Treatment-emergent adverse events (TEAEs) related to IXA were 43.0% and treatment-emergent serious adverse events (SAE) related to IXA were 4.4%. TEAEs leading to treatment discontinuation (temporary and permanent) were 7.9%. TEAEs leading to discontinuation of the study were 0.9%. SAEs leading to treatment discontinuation (temporary and permanent) were 2.6%. SAEs leading to discontinuation of the study were 0.9%. TEAE of special interest were 4.4%. TEAE with Outcome of Death is 1.8% (Table 2).

Conclusion: The interim analysis results show characteristics in pts receiving IXA in real-world clinical practice. The safety profile of IXA in Chinese patients is consistent with the TOURMALINE-MM1-China Continuation Study.

Fu:Takeda (China) International Trading Co, Ltd: Consultancy, Speakers Bureau. Zhou:Takeda (China) International Trading Co, Ltd: Speakers Bureau. Zhuang:Takeda (China) International Trading Co, Ltd: Consultancy, Speakers Bureau. Li:Takeda (China) International Trading Co, Ltd: Consultancy, Speakers Bureau. Fu:Takeda (China) International Trading Co, Ltd: Consultancy, Speakers Bureau. Zhang:Takeda (China) International Trading Co, Ltd: Speakers Bureau. Li:Takeda (China) International Trading Co., Ltd, Shanghai, China: Current Employment. Wu:Takeda (China) International Trading Co, Ltd: Consultancy, Speakers Bureau.